Cabozantinib: from studies to clinical practice

Матвеев, В. Б.; Ольшанская, А. С.; Волкова, М. И.

doi:10.17650/1726-9776-2019-15-3-28-41

Cited by 6 publications

(6 citation statements)

References 50 publications

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“…Досередины2000-хгодоввозможностилекарст-венноголеченияраспространенногоРПограничивалисьнеспецифическойиммунотерапиейпрепаратамиинтерфероновогоиинтерлейкиновогоряда, которыедемонстрировалинизкуюобщуюэффективность [7,8].Поэтомувпубликацияхтоговремени хирургиярассматриваласькакпрактическиединственныйметод,способныйзначительноувеличить выживаемостьприметастатическомпораженииПЖ [9].Ситуациякореннымобразомизмениласьпосле внедрениявклиническуюпрактикуновогокласса фармакологическихпрепаратов-таргетных,втом числеиммуноонкологическихагентов,эффективностькоторыхбыладоказанарезультатамикрупных рандомизированныхисследований [1].Сразвитием данногонаправлениялекарственнойтерапиицелесообразностьиспользованияхирургическогометода сталапредметомнаучнойдискуссии [10,11].…”

Section: Discussionunclassified

“…Насегодняшнийденьобщепринятымстандартом леченияраспространенногосветлоклеточногорака почки(РП)являетсясистемнаяфармакотерапия(ФТ) сиспользованиемтаргетных,втомчислеиммуноонкологическихагентов [1].Вместестем,согласно современнымрекомендациям,увыборочнойкатегориибольныхссолитарными(1узел)иединичными (2-3 узла) метастазами РП в качестве возможной лечебнойопцииможетприменятьсяхирургический метод [2][3][4].Поджелудочнаяжелеза(ПЖ),являясь редкой,носпецифичнойлокализациейолигометаста-тическогопрогрессированияРП,ассоцииро ванной снеагрессивным,индолентнымтечениемзаболевания [5,6],представляетбольшойнаучныйипрактический интерес для реализации данной альтернативной лечебнойтактики.Однакостандартизированныекритерииселекциипациентовдляхирургическоголеченияотсутствуют,ирешениеовыбореметодаконтроля заболеваниявкаждомконкретномслучаепринимаетсяиндивидуальномультидисциплинарнойкомандой. При этом порой возникают спорные клинические ситуации, в которых существенным препятствием длявыборахирургическогометодаявляетсяограниченностьданныхоегоэффективностипосравнению сФТ.…”

Section: Introductionunclassified

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Pancreatic metastases from renal cancer: comparing surgery and pharmacotherapy efficacy

et al. 2020

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Background. Today, targeted therapy is a standard treatment in advanced renal cell carcinoma, while the surgical method plays the role of a possible approach in a select category of patients with solitary and single metastases.The study objective to compare the effectiveness of two alternative treatment approaches: the surgical method and modern pharmacotherapy in achieving long-term overall survival of patients with pancreatic metastases of renal cell carcinoma.Materials and methods. A retrospective two-center study was conducted. The cohort of surgical treatment included patients (n = 56) who underwent surgery for pancreatic metastases from renal cell carcinoma at the N.N. Blokhin National Medical Research Center of Oncology and A.V. Vishnevsky National Medical Research Center of Surgery in the period from 1990 to 2019. Operations were performed for all types of pancreatic lesions: synchronous/metachronous, solitary/single and multiple, isolated/combined with lesions of other organs. Postoperative mortality rate was 5 % (3 patients). The pharmacotherapy cohort (n = 28) included patients with potentially resectable pancreatic metastases from clear cell renal cell carcinoma who underwent targeted therapy. Survival was assessed using the Kaplan–Mayer method. The Mantel–Cox test was used to test null hypothesis.Results. The 5-year overall survival rate was 68 % in the surgery group compared to 35 % for the pharmacotherapy group. Median overall survival for surgical and non-surgical patients was 82 months and 43 months, respectively (p = 0.01). The advantage of the surgical method was also found in a subgroup survival analysis of patients with extrapancreatic disease (p = 0.037). In this case, the 5-year overall survival rate was 66 % in the surgery subgroup (n = 25) compared to 35 % for the pharmacotherapy subgroup (n = 24). Conclusion. Radical surgical treatment in comparison with modern pharmacotherapy allows to achieve significantly higher rates of overall survival in patients with pancreatic metastases of renal cell carcinoma and can be considered as a priority.

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Section: Discussionunclassified

Section: Introductionunclassified

Pancreatic metastases from renal cancer: comparing surgery and pharmacotherapy efficacy

et al. 2020

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“…Кабозантиниб -ингибитор тирозинкиназных доменов ряда факторов роста, ангиогенеза, абнормального ремоделирования кости, метастазирования, а также лекарственной устойчивости. Кабозантиниб способен эффективно блокировать ряд мишеней при раке почки, таких как VEGFR1, 2 и 3, AXL и MET (рецептор фактора роста гепатоцитов), а также RET, рецептор фактора роста стволовых клеток KIT, FLT3, ROS1, MER, TYRO3, TRKB и TIE-2 [36][37][38].…”

Section: клинический случайunclassified

Renal cell carcinoma with metastases to the external genitalia. Literature review and case report

Menshikov

Султанбаев²,

Musin³

et al. 2021

Onkourologiâ

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Annually, up to 300 thousand new cases of kidney cancer and more than 134 thousand deaths associated with this disease are registered in the world. In the Russian Federation in 2019, 20,758 patients with a newly diagnosed renal cell carcinoma were registered; it should be noted that at the end of 2019, 177,755 patients with this diagnosis were registered. The issue of renal cell carcinoma metastasis seems to be quite relevant. The most common organs for metastatic renal cell carcinoma are lungs (up to 55 %), lymph nodes (up to 34 %), liver (up to 32 %), bones (up to 32 %), adrenal glands (up to 19 %), contralateral kidney (up to 11 %) and the brain (up to 5.7 %). The incidence of skin metastases in renal cell carcinoma ranges from 2.8 to 6.8 %, according to various authors.Our publication presents a case of treatment of a patient with a rare localization of renal cell carcinoma metastases in the external genital organs. The patient underwent palliative nephrectomy and vulvectomy. Taking into account the data on the prevalence of the disease, therapy with cabozantinib is carried out. Cabosantinib is an inhibitor of the tyrosine kinase domains of a number of growth factors, angiogenesis, abnormal bone remodeling, metastasis, and drug resistance.

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“…Изолированные периферические лимфоциты изучались непосредственно после выделения. Клетки инкубировали в течение 15 мин при 4°С с нормальными мышиными иммуноглобулинами (mIgG) (6 мкг мкг / 10 6 клеток) (Invitrogen, ThermoFisherScientific), затем инкубировали с меченными флуорохромом антителами к поверхностным антигенам в течение 30 мин при 4°С (FITC анти-CD45, клон HI30, PE анти-VEGFR2, клон 7D4- 6…”

Section: проточная цитометрияunclassified

Expression of Receptor Tyrosine Kinases on Peripheral Blood Lymphocyte Subpopulations in Patients with Renal Cell Carcinoma and Healthy Volunteers

Volkova¹,

Ольшанская²,

Хоченков

et al. 2020

Malignant Tumours

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Introduction: tyrosine kinases receptors (RTKs) play an important role in the pathogenesis of renal cell carcinoma (RCC). RTKs were studied on tumor and endothelial cells, but the presence of these receptors on lymphocytes was not confirmed. The objective of this study was to investigate the expression of tyrosine kinases receptors on lymphocyte subpopulations in healthy volunteers and RCC patients before and after removal of the primary tumor.Materials and methods: the study included 19 patients with pT1‑T3N0 / N+M0 / M+ RCC, subjected to nephrectomy, and 10 healthy volunteers. Blood samples were collected once from healthy donors and twice from RCC patients, immediately before and 180 days after surgery. Isolation of lymphocytes and flow cytometry were carried out using standard methods. A comparative analysis of RTKs expression levels in peripheral lymphocytes from healthy volunteers and RCC patients, as well as in RCC patients before and after the operation, was carried out. A search was performed for correlations between the initial RTKs expression on lymphocytes from RCC patients and characteristics of the tumor development, as well as the disease prognosis.Results: VEGFR-1, -2, -3, FGFR2, PDGFRα, β RTKs are expressed on CD45+ peripheral blood mononuclear cells, as well as subpopulations of CD3+ and CD8+ lymphocytes in healthy volunteers and untreated patients with RCC. No differences in the expression levels of all studied RTKs between subpopulations of lymphocytes were found in RCC patients (p > 0.05 for all). The level of RTKs expression on CD45+ peripheral cells in RCC patients before treatment is significantly lower than in healthy volunteers (p < 0.05 for all). The degree of a decrease in RTKs expression correlated with the pT status and the presence of tumor-associated venous thrombosis. A significant increase in the expression levels of VEGFR1 (on CB45+) and VEGFR2 (on CD8+, CD3+) (p < 0.05 for all) was noted 180 days after the removal of the primary tumor in patients with RCC. No other significant changes in RTKs production were identified. We were not able to determine the effect of RTKs expression on the RCC outcome.Conclusions: lymphocytes express RTKs, their expression is more pronounced in healthy people than in patients with RCC. After surgical treatment, the RTKs expression becomes restored.

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Cabozantinib: from studies to clinical practice

Cited by 6 publications

References 50 publications

Pancreatic metastases from renal cancer: comparing surgery and pharmacotherapy efficacy

Pancreatic metastases from renal cancer: comparing surgery and pharmacotherapy efficacy

Renal cell carcinoma with metastases to the external genitalia. Literature review and case report

Expression of Receptor Tyrosine Kinases on Peripheral Blood Lymphocyte Subpopulations in Patients with Renal Cell Carcinoma and Healthy Volunteers

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